Bortezomib, Pomalidomide, Dexamethasone for Systemic AL Amyloidosis

Phase 2

Recruiting

• Conditions: Systemic Amyloidosis
• Interventions: Drug: Bortezomib; Drug: Pomalidomide; Drug: Dexamethasone

• Registration Number: NCT06342466
• Lead Sponsor: Jin Lu, MD

Brief Summary

This is an open-label, multicenter, Phase 2 study in subjects with newly diagnosed or previous treated systemic light chain (AL) amyloidosis. Approximately 40 subjects will receive therapy with bortezomib, pomalidomide, and dexamethasone. The primary outcome is hematologic very good partial response and complete response rate at 6 months.

Detailed Description

Proteasome inhibitor and immunmodulators have synergistic effect for plasma cell dyscrasia. Due to the fact that more than 70-80% of patients with amyloidosis have renal involvement, the application of lenalidomide is limited. Thus, the investigators designed this open-label, multicenter, phase 2 study for newly diagnosed or previously treated systemic AL amyloidosis with bortezomib, pomalidomide and dexamethasone regimen.

Study Timeline

• Study First Submitted: 2024-03-19
• Study First Submitted QC: 2024-03-26
• Study First Posted: 2024-04-02
• Status Verified: 2024-05
• Study Start: 2024-05-06
• Last Update Submitted: 2024-12-25
• Last Update Posted: 2024-12-30
• Primary Completion: 2026-12
• Study Completion: 2026-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

1. Diagnosis of AL amyloidosis, confirmed by histology and typed with immunohistochemistry, immunoelectron microscopy or mass spectrometry.

2. Newly diagnosed or previous treated AL amyloidosis

3. Patients must be ≥ 18 years of age.

4. ECOG performance status 0, 1 or 2.

5. Measurable disease defined by at least one of the following:

   ① serum free light chain (FLC) ≥2.0 mg/dL (20 mg/L) with an abnormal kappa:lambda ratio or the difference between involved and uninvolved free light chains (dFLC) ≥2mg/dL (20 mg/L).

   ②. presence of a monoclonal spike that is ≥5 g/l.

6. Symptomatic organ involvement (heart, kidney, liver/GI tract, peripheral nervous system).

7. Absolute neutrophil count (ANC) ≥1.0 X 10^9/L, Hemoglobin ≥70 g/L, Platelets ≥50 X 10^9/L

8. eGFR ≥20 mL/min/ 1.73 m^2

9. Written informed consent in accordance with local and institutional guidelines.

10. Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

Exclusion Criteria

1. Fulfill with the criteria of active multiple myeloma or active lymphoplasmacytic lymphoma.
2. Presence of other tumors which is/are in advanced malignant stage and has/have systemic metastasis;
3. Severe or persistent infection that cannot be effectively controlled;
4. Presence of severe autoimmune diseases or immunodeficiency disease;
5. Patients with active hepatitis B or hepatitis C ([HBVDNA+] or [HCVRNA+]);
6. Patients with HIV infection or syphilis infection;
7. Any situations that the researchers believe will increase the risks for the subject or affect the results of the study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
BPd	Bortezomib	BPd regimen (Bortezomib, pomalidomide, and dexamethasone) will be applied every 28 days until progression of disease, unacceptable toxicity or subsequent therapy, for a maximum of six cycles.
BPd	Pomalidomide	BPd regimen (Bortezomib, pomalidomide, and dexamethasone) will be applied every 28 days until progression of disease, unacceptable toxicity or subsequent therapy, for a maximum of six cycles.
BPd	Dexamethasone	BPd regimen (Bortezomib, pomalidomide, and dexamethasone) will be applied every 28 days until progression of disease, unacceptable toxicity or subsequent therapy, for a maximum of six cycles.

Primary Outcome Measures

Name	Time	Method
Hematologic VGPR + CR rate at 6 months	6 months	Hematologic very good partial response plus complete response rate at 6 months

Secondary Outcome Measures

Name	Time	Method
TTNT at 2 years	2 years	Time to next treatment at 2 years
Overall Hematologic response rate at 6 months	6 months	Overall Hematologic partial response, very good partial response rate and complete response at 6 months
At least one organ response at 6 months	6 months	At least one organ response (cardiac response, renal response, liver response) at 6 months
TRAE	6 months	Treatment-related adverse events up to 6 months
Estimated PFS at 2 years	2 years	Estimated Progression free survival at 2 years
Estimated OS at 2 years	2 years	Estimated Overall Survival at 2 years

Trial Locations

Locations (1)

Peking University People's Hospital; 🇨🇳 Beijing, Beijing, China